CRCNS: Gamma Rhythms and Cell Assemblies

CRCNS：伽马节律和细胞组装

• 批准号: 7777645
• 负责人: NANCY KOPELL
• 金额: $ 35.29万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7777645
• 关键词: Affect; Agonist; Amygdaloid structure; Area; Attention; Auditory area; Autistic Disorder; Basal Ganglia; Basic Science; Behavior; Binding; Boston; Brain; Carbachol; Cell model; Cells; Cholecystokinin; Cholinergic Agonists; Cognitive; Collaborations; Computer Simulation; Consensus; Corpus striatum structure; D Cells; Defect; Disease; Electrophysiology (science); Epilepsy; Experimental Models; Fire - disasters; Frequencies; Functional disorder; Glutamates; Grant; Head; Hippocampus (Brain); Interneurons; Label; Lateral; Light; Link; Location; Measures; Mental disorders; Modeling; Molecular Biology; Motor; Motor Activity; Neocortex; Nervous System Part; Neurons; Optics; Parkinson Disease; Parvalbumins; Pathology; Phase; Physiologic pulse; Play; Positioning Attribute; Postdoctoral Fellow; Process; Property; Pyramidal Cells; Recording of previous events; Research; Research Personnel; Role; Schizophrenia; Science; Senior Scientist; Sensory Process; Short-Term Memory; Site; Slice; Somatostatin; Specificity; Symptoms; Synapses; Techniques; Time; Training; Work; cell assembly; cell type; cognitive function; entorhinal cortex; graduate student; in vitro Model; insight; kainate; mathematical model; member; memory recall; neocortical; network models; neural circuit; research study; response

DESCRIPTION (provided by applicant): Gamma frequency oscillations (30-90 Hz) are found in many parts of the nervous system, including the hippocampus, neocortex, entorhinal cortex and amygdala. They are believed to be important for a range of functions, including attention, early sensory processing, short term memory, motor activity. Mental illnesses, notably schizophrenia, are associated with pathologies in this rhythm, and many people are now studying these pathologies for clues to the pathophysiology of the diseases. At a simple level of description, gamma oscillations are thought to come about as interactions of parvalbumin positive (PV+) fast-spiking (FS) interneurons and pyramidal cells. However, it is known that other cell types, especially interneurons, participate in gamma rhythms and/or may modulate power and coherence of those rhythms. To understand the functional importance of these rhythms, it is necessary to better understand mechanisms that create and modulate them. Here we propose to use, for the first time, the combination of mathematical modeling with application of a set of emerging techniques involving molecular biology, optics, and electrophysiology to study the cell-type specific and circuitry properties of networks that produce gamma oscillations in the cortex. We will use in vitro models of the primary auditory cortex, with gamma oscillations induced using the glutamatergic agonist kainate or the cholinergic agonist carbachol. Specific classes of cells will be activated or suppressed by brief or longer periods of light. The work will focus on pyramidal cells, PV+ cells, cholecystokinin-expressing (CCK+) cells and somatostatin-containing (SOM+) interneurons. Minimal models will be constructed of these cells types and networks containing all of them. The model networks will be used to understand how the CCK+ and SOM+ interneurons interact with the PV+ cells to alter the gamma rhythms, in connection with experimental manipulations of the activity of different cell types. The experiments and models will also be used to understand how the CCK+ and SOM+ cells may affect the creation of cells assemblies. Broader Impacts: This work is part of a broader set of research by these labs on the importance of dynamics in cognitive function. The investigator is head of the Cognitive Rhythms Collaborative in the Boston area, a group of about 20 senior scientists, whose aim is to create and support new collaborations, including those making use of basic science and modeling in the study of disease, including Epilepsy, Parkinson's Disease, Autism and Schizophrenia. The work done in this project will provide new science that will interact with the work of many others in that group. The experimental work provides, for the first time, a combination of molecular biology, optics, and electrophysiology to study the cell-type specific and circuitry properties of networks; these techniques, pioneered by a member of this group, can then be used in many other contexts, beyond this group. The techniques and results will help provide information about the pathophysiology of mental illnesses; this has the potential of controlling such diseases by correcting the "oscillapathy" (defects in brain dynamics) associated with the symptoms. Finally, the specific project will also help train two graduate students and a postdoctoral fellow.

描述（由申请人提供）：在神经系统的许多部分中发现了伽马频率振荡（30-90 Hz），包括海马，新皮层，内嗅皮层和杏仁核。人们认为它们对于一系列功能很重要，包括注意力，早期感觉处理，短期记忆，运动活动。精神疾病，尤其是精神分裂症，与这种节奏中的病理学有关，许多人现在正在研究这些病理学，以了解疾病的病理生理学的线索。在简单的描述中，γ振荡被认为是白蛋白蛋白阳性（PV+）快速刺激（FS）中间神经元和金字塔细胞的相互作用。然而，众所周知，其他细胞类型，尤其是中间神经元也参与γ节奏和/或可能调节这些节奏的功率和连贯性。要了解这些节奏的功能重要性，有必要更好地理解创建和调节它们的机制。在这里，我们提议首次使用数学建模与应用一组涉及分子生物学，光学和电生理学的新兴技术的结合，以研究在皮质中产生γ振荡的网络的细胞类型特异性和电路性能。我们将使用原发性听觉皮层的体外模型，并使用谷氨酸能激动剂的乳腺癌或胆碱能激动剂卡尔巴乔（Carbachol）诱导γ振荡。特定类别的细胞将被短期或更长的光线激活或抑制。这项工作将集中于锥体细胞，PV+细胞，表达胆囊化的（CCK+）细胞和含母抑素的（SOM+）中间神经元。这些单元类型和包含所有这些细胞类型和网络将构建最小模型。模型网络将用于了解CCK+和SOM+中间神经元如何与PV+细胞相互作用以改变γ节律，这与对不同细胞类型活性的实验操作有关。实验和模型还将用于了解CCK+和SOM+细胞如何影响细胞组件的产生。更广泛的影响：这项工作是这些实验室对动态在认知功能中重要性的更广泛研究的一部分。研究者是波士顿地区认知节奏合作的负责人，这是一组大约20位高级科学家，其目的是创建和支持新的合作，包括那些在疾病研究中使用基础科学和建模的人，包括癫痫，帕金森氏病，自闭症，自闭症和精神分裂症。该项目中所做的工作将提供新科学，以与该小组中许多其他工作的工作相互作用。实验工作首次提供了分子生物学，光学和电生理学的组合，以研究网络的细胞类型特异性和电路特性。这些技术是由该组成员开创的，然后可以在此组以外的许多其他情况下使用。这些技术和结果将有助于提供有关精神疾病的病理生理学的信息；这具有通过纠正与症状相关的“示波器”（脑动力学缺陷）来控制此类疾病的潜力。最后，特定的项目还将帮助培训两名研究生和一名博士后研究员。